ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.749G>A (rs771614642)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230925 SCV000287192 uncertain significance Familial platelet disorder with associated myeloid malignancy 2020-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 250 of the RUNX1 protein (p.Arg250His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs771614642, ExAC 0.009%). This variant has not been reported in the literature in individuals with RUNX1-related disease. ClinVar contains an entry for this variant (Variation ID: 239055). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000230925 SCV000891084 uncertain significance Familial platelet disorder with associated myeloid malignancy 2021-01-12 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV001255168 SCV001431517 uncertain significance Acute myeloid leukemia 2020-08-17 criteria provided, single submitter clinical testing This RUNX1 variant (rs771614642) is rare (<0.1%) in a large population dataset (gnomAD: 11/281252 total alleles; 0.004%; no homozygotes) and has not been reported in the literature, to our knowledge. RUNX1 c.749G>A has been reported in ClinVar. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be tolerated. Due to insufficient evidence, we consider its clinical significance uncertain at this time.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.